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Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) accounts for nearly 50% of heart failure population. Unlike heart failure with reduced ejection fraction (HFrEF), the neurohumoral activity in HFpEF is incompletely studied. A recent clinical trial has suggested that β blockers were less beneficial to HFpEF than HFrEF, suggesting a different neurohumoral milieu between them. Previously, we have demonstrated that deoxycorticosterone acetate (DOCA) -salt hypertensive mice develop diastolic dysfunction (DD) with preserved EF. These mice have a significantly lower baseline heart rate (HR). We reasoned that sympathetic activity would be reduced in DD as opposed to the general observation in HFrEF.

Methods: DOCA mice were produced by uninephrectomy, DOCA pellet subcutaneous implantation and 1% saline drinking water. Surface ECG and invasive electrophysiology study were performed in isoflurane anesthetized mice. HR variability (HRV) was measured in the frequency and time domains. Arrhythmia was induced by burst pacing and programming stimulation.

Results: Compared to sham mice, DOCA mice had longer RR interval and slower AV conduction, consistent with parasympathetic activation. The total power in the HRV measurement was higher in DOCA mice with the most prominent elevation in low frequency power. All the time-domain parameters were higher in DOCA mice compared to sham mice (See Table 1). Ventricular tachycardia (VT) and supraventricular tachycardia (SVT, 15% higher HR than baseline) were induced in 3 out of 7 sham mice respectively. In contrast, no DOCA mice (n=7) had VT (p=0.05) or SVT (p=0.05) episodes, indicating improved cardiac electrical stability possibly by enhanced parasympathetic tone. Moreover, type I 2° AV block was found in 1 DOCA mouse.

Conclusion: Sympathetic activity appears reduced and parasympathetic activity increased in diastolic dysfunction, which could be a reason that β blockers are less effective in HFpEF.